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WO2023250339A3 - Vla4 inhibitors and uses thereof - Google Patents

Vla4 inhibitors and uses thereof Download PDF

Info

Publication number
WO2023250339A3
WO2023250339A3 PCT/US2023/068760 US2023068760W WO2023250339A3 WO 2023250339 A3 WO2023250339 A3 WO 2023250339A3 US 2023068760 W US2023068760 W US 2023068760W WO 2023250339 A3 WO2023250339 A3 WO 2023250339A3
Authority
WO
WIPO (PCT)
Prior art keywords
methods
vla
present disclosure
inhibitors
chemokine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2023/068760
Other languages
French (fr)
Other versions
WO2023250339A2 (en
Inventor
Peter Ruminski
John DIPERSIO
Michael RETTIG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Washington University in St Louis WUSTL
Original Assignee
Washington University in St Louis WUSTL
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Washington University in St Louis WUSTL filed Critical Washington University in St Louis WUSTL
Priority to AU2023289375A priority Critical patent/AU2023289375A1/en
Priority to EP23827996.2A priority patent/EP4543495A2/en
Priority to JP2024575346A priority patent/JP2025523498A/en
Priority to CA3260419A priority patent/CA3260419A1/en
Publication of WO2023250339A2 publication Critical patent/WO2023250339A2/en
Publication of WO2023250339A3 publication Critical patent/WO2023250339A3/en
Anticipated expiration legal-status Critical
Priority to MX2025000268A priority patent/MX2025000268A/en
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present disclosure provides therapeutic agents comprising VLA-4 (a4b1) and a4b?inhibiting agents defined herein. Methods of using the therapeutic agents are also provided. The present disclosure further provides combinations of a VLA-4 inhibitor and one or more agents which interact with a chemokine receptor or chemokine receptors, and methods of use thereof. In some embodiments, the disclosed combinations may be used in a method of mobilizing hematopoietic stem cells. In some embodiments, the disclosed methods may be used in the treatment of a condition that requires the collection of hematopoietic stem cells for transfusions or in chemotherapy. The present disclosure further provides methods of treating a patient comprising administering an agent which interacts with a chemokine such as G-CSF, plerixafor, BL-8040 (Motixafortide), or Crop and VLA-4 inhibitors.
PCT/US2023/068760 2022-06-21 2023-06-21 Vla4 inhibitors and uses thereof Ceased WO2023250339A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AU2023289375A AU2023289375A1 (en) 2022-06-21 2023-06-21 Vla4 inhibitors and uses thereof
EP23827996.2A EP4543495A2 (en) 2022-06-21 2023-06-21 Vla4 inhibitors and uses thereof
JP2024575346A JP2025523498A (en) 2022-06-21 2023-06-21 VLA4 inhibitors and uses thereof
CA3260419A CA3260419A1 (en) 2022-06-21 2023-06-21 Vla4 inhibitors and uses thereof
MX2025000268A MX2025000268A (en) 2022-06-21 2025-01-06 Vla4 inhibitors and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263353947P 2022-06-21 2022-06-21
US63/353,947 2022-06-21

Publications (2)

Publication Number Publication Date
WO2023250339A2 WO2023250339A2 (en) 2023-12-28
WO2023250339A3 true WO2023250339A3 (en) 2024-03-14

Family

ID=89380653

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2023/068760 Ceased WO2023250339A2 (en) 2022-06-21 2023-06-21 Vla4 inhibitors and uses thereof

Country Status (6)

Country Link
EP (1) EP4543495A2 (en)
JP (1) JP2025523498A (en)
AU (1) AU2023289375A1 (en)
CA (1) CA3260419A1 (en)
MX (1) MX2025000268A (en)
WO (1) WO2023250339A2 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160310612A1 (en) * 2013-10-15 2016-10-27 Seattle Genetics, Inc. Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics
US20190328706A1 (en) * 2016-11-02 2019-10-31 Saint Louis University Compositions comprising an integrin inhibitor and agents which interact with a chemokine and methods of use thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160310612A1 (en) * 2013-10-15 2016-10-27 Seattle Genetics, Inc. Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics
US20190328706A1 (en) * 2016-11-02 2019-10-31 Saint Louis University Compositions comprising an integrin inhibitor and agents which interact with a chemokine and methods of use thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KARPOVA DARJA, RETTIG MICHAEL P., RITCHEY JULIE, CANCILLA DANIEL, CHRIST STEPHANIE, GEHRS LEAH, CHENDAMARAI EZHILARASI, EVBUOMWAN : "Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells", JOURNAL OF CLINICAL INVESTIGATION, vol. 129, no. 7, 1 July 2019 (2019-07-01), pages 2745 - 2759, XP093149710, ISSN: 0021-9738, DOI: 10.1172/JCI124738 *
KROHN-GRIMBERGHE, M ET AL.: "Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem- cell niche", NATURE BIOMEDICAL ENGINEERING, vol. 4, 11 November 2020 (2020-11-11), pages 1076 - 1089, XP037288408, DOI: 10.1038/s41551-020-00623-7 *
MURPHY, AJ ET AL.: "Pegylation of High-Density Lipoprotein Decreases Plasma Clearance and Enhances Antiatherogenic Activity", CIRCULATION RESEARCH, vol. 113, no. 1, 21 June 2013 (2013-06-21), pages e1 - e9, XP055147084, DOI: 10.1161/CIRCRESAHA.113.301112 *

Also Published As

Publication number Publication date
EP4543495A2 (en) 2025-04-30
CA3260419A1 (en) 2023-12-28
JP2025523498A (en) 2025-07-23
AU2023289375A1 (en) 2025-01-16
WO2023250339A2 (en) 2023-12-28
MX2025000268A (en) 2025-04-02

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